A Comparison of High and Usual Protein Dosing in Critically Ill Patients With Obesity: A Post Hoc Analysis of an International, Pragmatic, Single-Blinded, Randomized Clinical Trial.

OBJECTIVES: Across guidelines, protein dosing for critically ill patients with obesity varies considerably. The objective of this analysis was to evaluate whether this population would benefit from higher doses of protein. DESIGN: A post hoc subgroup analysis of the effect of higher protein dosing in critically ill patients with high nutritional risk (EFFORT Protein): an international, multicenter, pragmatic, registry-based randomized trial. SETTING: Eighty-five adult ICUs across 16 countries. PATIENTS: Patients with obesity defined as a body mass index (BMI) greater than or equal to 30 kg/m 2 ( n = 425). INTERVENTIONS: In the primary study, patients were randomized into a high-dose (≥ 2.2 g/kg/d) or usual-dose protein group (≤ 1.2 g/kg/d). MEASUREMENTS AND MAIN RESULTS: Protein intake was monitored for up to 28 days, and outcomes (time to discharge alive [TTDA], 60-d mortality, days of mechanical ventilation [MV], hospital, and ICU length of stay [LOS]) were recorded until 60 days post-randomization. Of the 1301 patients in the primary study, 425 had a BMI greater than or equal to 30 kg/m 2 . After adjusting for sites and covariates, we observed a nonsignificant slower rate of TTDA with higher protein that ruled out a clinically important benefit (hazard ratio, 0.78; 95% CI, 0.58-1.05; p = 0.10). We found no evidence of difference in TTDA between protein groups when subgroups with different classes of obesity or patients with and without various nutritional and frailty risk variables were examined, even after the removal of patients with baseline acute kidney injury. Overall, 60-day mortality rates were 31.5% and 28.2% in the high protein and usual protein groups, respectively (risk difference, 3.3%; 95% CI, -5.4 to 12.1; p = 0.46). Duration of MV and LOS in hospital and ICU were not significantly different between groups. CONCLUSIONS: In critically ill patients with obesity, higher protein doses did not improve clinical outcomes, including those with higher nutritional and frailty risk.

Prebiotics in the management of pediatric gastrointestinal disorders: Position paper of the ESPGHAN special interest group on gut microbiota and modifications.

Prebiotics are substrates that are selectively utilized by host microorganisms conferring a health benefit. Compared to probiotics there are few studies with prebiotics in children. Most studies have been performed using infant formula supplemented with prebiotics, while add-on prebiotic supplementation as prevention or treatment of childhood gastrointestinal disorders has rarely been reported. The aim of this position paper was to summarize evidence and make recommendations for prebiotic supplementation in children with gastrointestinal diseases. Recommendations made are based on publications up to January 1, 2023. Within the scope of the European Society for Paediatric Gastroenterology Hepatology and Nutrition Special Interest Group on Gut Microbiota and Modifications, as in our previous biotic recommendations, at least two randomized controlled clinical trials were required for recommendation. There are some studies showing benefits of prebiotics on selected outcomes; however, we cannot give any positive recommendations for supplementing prebiotics in children with gastrointestinal disorders.

Reevaluating the FDA's warning against the use of probiotics in preterm neonates: A societal statement by ESPGHAN and EFCNI.

The recent advisory issued by the United States Food and Drug Administration, cautioning against the routine administration of probiotics in preterm neonates, has sparked a lively debate within the scientific community. This commentary presents a perspective from members of the Special Interest Group on Gut Microbiota and Modifications within the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and other authors who contributed to the ESPGHAN position paper on probiotics for preterm infants, as well as representatives from the European Foundation for the Care of Newborn Infants. We advocate for a more nuanced and supportive approach to the use of certain probiotics in this vulnerable population, balancing the demonstrated benefits and risks.

The Giardial Arginine Deiminase Participates in Giardia-Host Immunomodulation in a Structure-Dependent Fashion via Toll-like Receptors.

Beyond the problem in public health that protist-generated diseases represent, understanding the variety of mechanisms used by these parasites to interact with the human immune system is of biological and medical relevance. Giardia lamblia is an early divergent eukaryotic microorganism showing remarkable pathogenic strategies for evading the immune system of vertebrates. Among various multifunctional proteins in Giardia, arginine deiminase is considered an enzyme that plays multiple regulatory roles during the life cycle of this parasite. One of its most important roles is the crosstalk between the parasite and host. Such a molecular "chat" is mediated in human cells by membrane receptors called Toll-like receptors (TLRs). Here, we studied the importance of the 3D structure of giardial arginine deiminase (GlADI) to immunomodulate the human immune response through TLRs. We demonstrated the direct effect of GlADI on human TLR signaling. We predicted its mode of interaction with TLRs two and four by using the AlphaFold-predicted structure of GlADI and molecular docking. Furthermore, we showed that the immunomodulatory capacity of this virulent factor of Giardia depends on the maintenance of its 3D structure. Finally, we also showed the influence of this enzyme to exert specific responses on infant-like dendritic cells.

Multilevel Approach for the Treatment of Giardiasis by Targeting Arginine Deiminase.

Giardiasis represents a latent problem in public health due to the exceptionally pathogenic strategies of the parasite Giardia lamblia for evading the human immune system. Strains resistant to first-line drugs are also a challenge. Therefore, new antigiardial therapies are urgently needed. Here, we tested giardial arginine deiminase (GlADI) as a target against giardiasis. GlADI belongs to an essential pathway in Giardia for the synthesis of ATP, which is absent in humans. In silico docking with six thiol-reactive compounds was performed; four of which are approved drugs for humans. Recombinant GlADI was used in enzyme inhibition assays, and computational in silico predictions and spectroscopic studies were applied to follow the enzyme's structural disturbance and identify possible effective drugs. Inhibition by modification of cysteines was corroborated using Ellman's method. The efficacy of these drugs on parasite viability was assayed on Giardia trophozoites, along with the inhibition of the endogenous GlADI. The most potent drug against GlADI was assayed on Giardia encystment. The tested drugs inhibited the recombinant GlADI by modifying its cysteines and, potentially, by altering its 3D structure. Only rabeprazole and omeprazole decreased trophozoite survival by inhibiting endogenous GlADI, while rabeprazole also decreased the Giardia encystment rate. These findings demonstrate the potential of GlADI as a target against giardiasis.

Importancia de la suplementación en el embarazo: papel de la suplementación con hierro, ácido fólico, calcio, vitamina D y multivitamínicos.

Health promotion and disease prevention are essential components of prenatal care. Maternal nutrient insufficiencies could negatively impact the morbidity and mortality of the mother-fetus pair as well as the health of the next generations. Although a healthy diet is usually sufficient to meet the increased nutrient needs, supplementation is part of routine care to ensure a healthy pregnancy and optimal fetal development. Currently, iron and folic acid supplementation is the only globally accepted recommendation for all pregnant women. However, there are vulnerable groups of women who could benefit from complementary individualized supplementation schemes. Recently, relevant information has been published related to the supplementation of single and multiple micronutrients with significant effects on maternal and fetal health, which could have implications in the clinical practice of health professionals. This review presents scientific evidence and the recommendations of different entities on the supplementation of iron, folic acid, calcium, vitamin D and multiple micronutrient supplementation during pregnancy.

La promoción de la salud y la prevención de enfermedades son componentes esenciales de la atención prenatal. Las insuficiencias de nutrimentos afectan negativamente la morbimortalidad del binomio madre-hijo, así como a la salud de las siguientes generaciones. Aunque una alimentación saludable generalmente es suficiente para cubrir las necesidades aumentadas de micronutrimentos, la suplementación es parte del cuidado habitual para garantizar un embarazo saludable y el desarrollo óptimo del producto. Actualmente la suplementación de hierro y ácido fólico es la única recomendación mundialmente aceptada para todas las mujeres embarazadas. Por otro lado, existen grupos de mujeres vulnerables que podrían beneficiarse de esquemas de suplementación individualizados complementarios. Recientemente se ha publicado información relevante relacionada con la suplementación de distintos micronutrimentos de forma individual y múltiple con efectos importantes en la salud materno-fetal, lo cual podría tener implicaciones en la práctica clínica de los profesionales de la salud. Esta revisión presenta la evidencia científica y las recomendaciones de distintos organismos sobre la suplementación de hierro, ácido fólico, calcio, vitamina D y suplementación múltiple de vitaminas y minerales durante el embarazo.

Importancia de la vitamina B12 y el folato en la salud perinatal.

Fetal development is characterized by great plasticity and the ability to respond to environmental factors, where DNA methylation is essential for proper embryonic development. One-carbon metabolism provides methyl groups for methylation and fetal DNA development and is highly dependent on maternal nutritional status. During pregnancy, the supply of methyl donors is critical and the demand for nutrients that support this process, such as folate and vitamin B12, is increased. Insufficiency or imbalance of these 2 micronutrients can alter epigenetic patterns, DNA synthesis and repair, and affect fetal growth and development, having negative long-term consequences on the offspring's health. Folate and vitamin B12 status have been associated with wide DNA methylation, as well as with specific genes related to neurological functions, embryonic development, energy metabolism, growth, and leptin. Furthermore, inadequate concentrations of both vitamins have been associated with an increased risk of perinatal outcomes such as neural tube defects, prematurity, low birth weight, pre-eclampsia, as well as maternal and infant obesity and insulin resistance, and decreased infant neurocognitive development. Supplementation, combined with a healthy diet, could be an essential strategy to prevent these results and improve maternal and fetal health.

El desarrollo fetal se caracteriza por una gran plasticidad y capacidad para responder a factores ambientales, donde la metilación del ADN es indispensable para el desarrollo embrionario adecuado. El metabolismo de un carbono proporciona grupos metilo para la metilación y el desarrollo del ADN fetal, y depende en gran medida del estado nutricio materno. El embarazo es una etapa donde el suministro de donantes de metilo es crítico y la demanda de nutrimentos que apoyen este proceso, como lo son el folato y la vitamina B12, está aumentada. La insuficiencia o desequilibrio de estos dos micronutrimentos puede alterar los patrones epigenéticos, la síntesis y reparación del ADN, y afectar procesos del crecimiento y desarrollo fetal, teniendo consecuencias negativas en la salud de la descendencia a largo plazo. El estado del folato y la vitamina B12 se han asociado con la metilación global del ADN, así como con genes específicos relacionados con funciones neurológicas, con el desarrollo embrionario, el metabolismo energético, el crecimiento, y con la leptina. Además, estados alterados de ambas vitaminas se han asociado con mayor riesgo de resultados perinatales como defectos del tubo neural, prematurez, bajo peso al nacer, preeclampsia, así como obesidad y resistencia a la insulina materna e infantil, y disminución del desarrollo neurocognitivo infantil. La suplementación, aunada a una dieta adecuada, podría ser una estrategia necesaria para prevenir dichos resultados y mejorar la salud maternofetal.

Microbiota de la leche humana y su impacto en la salud humana.

Breast milk is a complex biological fluid. Additionally to its nutritional impact, it contains diverse bioactive elements related to early metabolic programming and molecular structures, such as microRNA related to the epigenetic signaling process. Now, we know that human milk is not sterile and contains a significant diversity of microorganisms such as bacteria (bacterioma), viruses (viroma) and fungi (mycobiome), all of which integrate the concept of the human milk microbiota. Apparently the origin of this microbiota is found in the entero-mammary circulation, as well as in the retrograde circulation of the skin of the mammary gland, although it is speculated in what percentage the microbiota of the oral cavity of the infant contributes in a significant way. From a functional point of view, it has been shown the transfer of this microbiota to the infant's digestive tract, which is related to better digestive tolerance, lower frequency and intensity of dysfunctionalities of the brain-intestine-microbiota axis, and improved immunity, among others.

La leche materna es un fluido biológico complejo, ya que además de nutrir, contiene diversos elementos bioactivos relacionados con el fenómeno de programación metabólica temprana e incluso contiene estructuras moleculares relacionadas con el proceso de señalización epigenética tales como los microARN. Ahora sabemos que la leche humana no es estéril y contiene una diversidad significativa de microorganismos tales como bacterias (bacterioma), virus (viroma) y hongos (micobioma), todo lo cual integra el concepto de microbiota de leche humana. Al parecer el origen de esta microbiota se encuentra en la circulación enteromamaria, así como en la circulación retrógrada de la piel de glándula mamaria, aunque se especula en qué porcentaje la microbiota de la cavidad bucal del lactante contribuye de forma significativa. Desde el punto de vista funcional, se ha demostrado transferencia de esta microbiota hacia el tubo digestivo del lactante, lo que se relaciona con una mejor tolerancia digestiva, menor frecuencia e intensidad de disfuncionalidades del eje cerebro-intestino-microbiota, y mejora de la inmunidad, entre otras.

Suplementos nutricionales para prevención de diabetes mellitus gestacional: lecciones aprendidas basadas en la evidencia.

INTRODUCTION: Gestational diabetes mellitus (GDM) affects between 5 and 40% of pregnant women. Recently different interventions with nutritional supplements have been evaluated for prevention of GDM. AIM: To perform a synthesis of the evidence on the efficacy of nutritional supplements (myo-inositol, probiotics, and vitamin D) in the prevention of GDM. METHODS: A systematic search in PubMed and Cochrane library was performed, including systematic reviews of randomized clinical trials (RCTs), published in English or Spanish until May 2020, using the keywords: "prevention", "gestational diabetes", "hyperglycemia and pregnancy", "supplementation", "probiotics", "myo-inositol" and "vitamin D". RESULTS: 10 systematic reviews that met the inclusion criteria were analyzed. Myo-inositol supplementation compared to placebo decreased the incidence of GDM (RR: 0.44 [0.27-0.87]; five RCTs), low quality of evidence. Although the supplementation with vitamin D or probiotics during pregnancy could reduce the incidence of GDM the evidence is limited. CONCLUSIONS: Myo-inositol supplementation is effective for prevention of GDM in high-risk women. Supplementation with vitamin D or probiotics probably decreases the incidence of GDM.

INTRODUCTION: La diabetes mellitus gestacional (DMG) afecta a entre el 5 y el 40% de mujeres embarazadas. Recientemente se han evaluado diferentes intervenciones con suplementos nutricionales para prevenir la DMG. OBJETIVO: Realizar una síntesis de la evidencia sobre eficacia de suplementos nutricionales (mioinositol, probióticos y vitamina D) para prevenir DMG. MÉTODO: Se realizó una búsqueda sistemática en PubMed y la biblioteca Cochrane, se incluyeron revisiones sistemáticas de estudios clínicos aleatorizados (ECAs), publicados en idioma inglés o español hasta mayo de 2020; se utilizaron las palabras clave: "prevención", "diabetes gestacional", "hiperglicemia y embarazo", "suplementación", "probióticos", "mio-inositol" y "vitamina D". RESULTADOS: Se analizaron 10 revisiones sistemáticas que cumplieron los criterios de inclusión. La suplementación con mioinositol comparado con placebo disminuyó la incidencia de DMG (RR: 0.44; IC 95%: 0.27-0.87; cinco ECAs). Si bien la suplementación con vitamina D o probióticos durante el embarazo podría disminuir la incidencia de DMG, la evidencia es limitada. CONCLUSIONES: La suplementación con mioinositol es efectiva para prevenir DMG en mujeres de alto riesgo. La suplementación con vitamina D o probióticos probablemente disminuye la incidencia de DMG.

Impacto de la suplementación con ácidos grasos omega-3 en el embarazo y la reducción del riesgo de parto pretérmino.

Preterm labor accounts for more than 85% of perinatal morbidity, frequently requiring intensive care and presenting complications that can have consequences throughout the individual's life. More than half of preterm delivery cases have unknown causes and therefore no clear preventable etiology. From observation in epidemiological studies that demonstrated longer pregnancies in populations with high consumption of marine oils, attempts have been made to define the benefit of omega-3 polyunsaturated fatty acids (n-3 PUFA) prevention in premature childbirth through randomized clinical trials, as well as its preventive value. This review discusses the relationship between prenatal supplementation of n-3 long chain PUFA during pregnancy and the incidence of preterm delivery.

El parto prematuro protagoniza más del 85% de la morbilidad perinatal, requiere con frecuencia cuidados intensivos y presenta complicaciones que pueden tener consecuencias a lo largo de la vida del individuo. Más de la mitad de los casos de parto pretérmino tienen causas desconocidas y por lo tanto ninguna etiología clara prevenible. Desde la observación en estudios epidemiológicos que demostraron embarazos más largos en poblaciones con alto consumo de aceites marinos se ha tratado de definir por medio de ensayos clínicos aleatorizados el beneficio de suplementos de ácidos grasos poliinsaturados omega-3 (AGPI n-3) prevenir el parto prematuro, así como su valor preventivo. Esta revisión discute la relación entre la suplementación prenatal de n-3 de cadena larga durante el embarazo y la incidencia de parto prematuro.

Factors associated with death in children with COVID-19 in Mexico.

INTRODUCTION: Most children affected by SARS-CoV-2 are reported to be asymptomatic, and COVID-19-related mortality in them is low; in Mexico, there is a lack of information on the subject in this population group. OBJECTIVE: To assess the risk factors associated with mortality in Mexican children with COVID-19. METHOD: Secondary analysis of the General Directorate of Epidemiology database. Children younger than 19 years, in whom SARS-CoV-2 infection was confirmed by RT-PCR, were included. RESULTS: 1443 children were included. Median age was eight years; 3.3 % were admitted to the intensive care unit, 1.8 % required assisted mechanical ventilation, and mortality was 1.9 %. In multivariate models, the development of pneumonia was the main risk factor for mortality, with an odds ratio (OR) of 6.45 (95 % CI: 1.99, 20.89); patients who required intubation had an OR of 8.75 (95 % CI: 3.23, 23.7). CONCLUSIONS: Children with COVID-19 exhibit high mortality in Mexico, and avoiding pneumonia should therefore be tried in them, especially in children younger than four years, with cardiovascular risk or immunosuppression. INTRODUCCIÓN: Se informa que la mayoría de los niños afectados por SARS-CoV-2 cursan asintomáticos y que en ellos la mortalidad por COVID-19 es baja; en México se desconoce la información al respecto en este grupo de la población. ­. OBJETIVO: Evaluar los factores de riesgo asociados a mortalidad en niños mexicanos con COVID-19. MÉTODO: Análisis secundario de la base de datos de la Dirección General de Epidemiología. Se incluyeron niños menores de 19 años, en quienes se confirmó SARS-CoV-2 mediante RT-PCR. RESULTADOS: Se incluyeron 1443 niños. La mediana de edad fue de ocho años; 3.3 % ingresó a la unidad de cuidados intensivos, 1.8 % requirió ventilación mecánica asistida y la mortalidad fue de 1.9 %. En los modelos multivariados, el desarrollo de neumonía constituyó el principal factor de riesgo de mortalidad, con razón de momios (RM) de 6.45 (IC 95 % 1.99, 20.89); los pacientes que requirieron intubación tuvieron RM de 8.75 (IC 95 % 3.23, 23.7). CONCLUSIONES: Los niños con COVID 19 tienen alta mortalidad en México, por lo que en ellos se debe procurar evitar la neumonía, especialmente en los menores de cuatro años, con riesgo cardiovascular o inmunosupresión.

Scientific medical journals in Mexico.

This symposium describes the main characteristics of six Mexican scientific journals indexed in Journal Citation Reports: Archives of Medical Research, Revista de Investigación Clínica-Clinical and Translational Investigation, Gaceta Médica de México, Salud Pública de México, Cirugía y Cirujanos and Salud Mental. Particular emphasis is given to their historical and organizational aspects, as well as to their main achievements recognized by the national and international scientific community.En este simposio se describen las principales características de seis revistas científicas mexicanas reconocidas por el. Journal Citation Reports: Archives of Medical Research, Revista de Investigación Clínica-Clinical and Translational Investigation, Gaceta Médica de México, Salud Pública de México, Cirugía y Cirujanos y Salud Mental. Se hace énfasis en sus aspectos históricos y organizacionales, así como en sus logros principales ante la comunidad científica nacional e internacional.

[Recomendaciones sobre la utilización de las fórmulas infantiles con proteína aislada de soya en la alimentación del lactante. Documento de posición basado en la evidencia].

BACKGROUND: Soy infant formulas (SIF) have long been used as an alternative for infants with special nutritional requirements. However, the medical indications for their use, their allergenicity, safety and efficacy are still controversial. OBJECTIVE: To present recommendations for the use of SIF based on the existing literature. METHODS: We consulted systematic reviews and clinical practice guides, through validated search algorithms, and systems such as Appraisal of Guidelines for REsearch and Evaluation (AGREE)II and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). For the elaboration of the clinical recommendations, the most important topics were analyzed and discussed by the responsible researchers and the group of experts in the development of a position paper. The quality of the evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. RESULTS: Several reports with variable quality of evidence were found. They support SIF's efficacy in the management of cow's milk allergy and infant's digestive tolerance, as well as its low cross allergy compared to cow's milk and other formulas. We also found other studies that indicate the safety of SIFs on different nutritional, immune and developmental parameters. There is also evidence that demonstrates that SIFs have important advantages in terms of cost-benefit, palatability and effects on the intestinal microbiota, compared to other formulas. CONCLUSIONS: Although evidence to recommend its use in functional digestive disorders is limited, SIFs have an adequate safety profile and are still a valid option for infant feeding.

ANTECEDENTES: Las fórmulas a base de proteína de soya (FBPS) se han utilizado desde hace tiempo como una alternativa para lactantes con requerimientos nutricionales especiales. Sin embargo, las indicaciones médicas para su uso, su alergenicidad, seguridad y eficacia aún son controvertidas. OBJETIVO: Presentar recomendaciones del uso de FBPS basadas en la literatura existente. MÉTODOS: Se realizó la consulta de revisiones sistemáticas y guías de práctica clínica, por medio de algoritmos de búsqueda validados, y sistemas como AGREE (Appraisal of Guidelines for REsearch and Evaluation) II y PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Para la elaboración de las recomendaciones clínicas se analizaron y discutieron los tópicos de mayor importancia, por parte de los investigadores responsables y el grupo de expertos del desarrollo de un documento de posición. Se evaluó la calidad de la evidencia utilizando el sistema GRADE (Grading of Recommendations, Assessment, Development and Evaluation). RESULTADOS: Se encontraron distintos reportes con calidad de evidencia variable que sustentan la eficacia de las FBPS en el manejo de la alergia a la proteína de la leche de vaca y en la tolerancia digestiva del lactante, así como su baja alergia cruzada en comparación a la leche de vaca y otras fórmulas. También se encontraron otros estudios que indican la seguridad de las FBPS sobre distintos parámetros nutricionales, inmunitarios y de desarrollo. Existe además evidencia que demuestra que las FBPS tienen ventajas importantes en cuestión de costo-beneficio, palatabilidad y efectos sobre la microbiota intestinal, en comparación con otras fórmulas. CONCLUSIONES: Aunque existe evidencia limitada para recomendar su utilización en los trastornos digestivos funcionales, las FBPS tienen un perfil de seguridad adecuado y continúan siendo una opción válida para la alimentación del lactante.

Proton pump inhibitors drastically modify triosephosphate isomerase from Giardia lamblia at functional and structural levels, providing molecular leads in the design of new antigiardiasic drugs.

BACKGROUND: Proton pump inhibitors (PPIs) are extensively used in clinical practice because of their effectiveness and safety. Omeprazole is one of the best-selling drugs worldwide and, with other PPIs, has been proposed to be potential drugs for the treatment of several diseases. We demonstrated that omeprazole shows cytotoxic effects in Giardia and concomitantly inactivates giardial triosephosphate isomerase (GlTIM). Therefore, we evaluated the efficiency of commercially available PPIs to inactivate this enzyme. METHODS: We assayed the effect of PPIs on the GlTIM WT, single Cys mutants, and the human counterpart, following enzyme activity, thermal stability, exposure of hydrophobic regions, and susceptibility to limited proteolysis. RESULTS: PPIs efficiently inactivated GlTIM; however, rabeprazole was the best inactivating drug and was nearly ten times more effective. The mechanism of inactivation by PPIs was through the modification of the Cys 222 residue. Moreover, there are important changes at the structural level, the thermal stability of inactivated-GlTIM was drastically diminished and the structural rigidity was lost, as observed by the exposure of hydrophobic regions and their susceptibility to limited proteolysis. CONCLUSIONS: Our results demonstrate that rabeprazole is the most potent PPI for GlTIM inactivation and that all PPIs tested have substantial abilities to alter GITIM at the structural level, causing serious damage. GENERAL SIGNIFICANCE: This is the first report demonstrating the effectiveness of commercial PPIs on a glycolytic parasitic enzyme, with structural features well known. This study is a step forward in the use and understanding the implicated mechanisms of new antigiardiasic drugs safe in humans.

[Characterization of adolescents and reason for the visit when attending the pediatric emergency department of the General Hospital Dr. Manuel Gea González]. / Caracterización de los adolescentes y motivo de consulta por el que acuden al Servicio de Urgencias Pediátricas del Hospital General Dr. Manuel Gea González.

RATIONALE: Emergency health care demanded by adolescents has increased due to a variety of specific disorders. AIMS: (1) Describe the frequency of emergency services utilization by adolescents; (2) Identify the reason for the visit; (3) Describe psychosocial and health features of patients; and (4) Describe information related to informed assent. MATERIAL AND METHODS: Observational, descriptive, and prospective study carried out in patients aged 12 to 18 years, treated in the emergency department of General Hospital "Dr. Manuel Gea Gonzalez ", between 2008 and 2009. Survey data as well as the HEADSS sociodemographic questionnaire was used. RESULTS: A total of 170 patients were included in the study. The average age was 14.1 years; 55% were female. The main reasons for consultation were trauma (32.9%), followed by non-surgical gastrointestinal pathologies (12.4%), acute abdomen (11.8%), psychiatric emergencies (10.6%), neurological (8.8%), infectious or gynecologic obstetrical (both 8.2%). In 81% of cases, relatives (mostly parents) were the ones who decided to take the patient to the emergency room. It is noteworthy that in 64% of cases the patients had previously gone to the emergency room. Of the patients, 72.4% reported not having regular medical care and the remaining reported that medical care was referred to once or twice a year. CONCLUSIONS: Among patients seeking emergency care, a significant proportion are teenagers. The causes are varied, with care ranging from posttraumatic aspects to psycho-behavioral disorders. There is minimal culture in this age group to agree about their own treatment through informed consent.

[Efficacy and safety of ciprofloxacin treatment in urinary tract infections (UTIs) in adults: a systematic review with meta-analysis]. / Eficacia y seguridad de la ciprofloxacina en el tratamiento de las infecciones de las vías urinarias (IVU) en adultos: revisión sistemática con metaanálisis.

OBJECTIVES AND DESIGN: A systematic review with meta-analysis of randomized controlled trials (RGT) on the efficacy and safety of ciprofloxacin in the treatment of acute or complicated urinary tract infections in adults. Primary outcomes were bacteriological eradication, clinical cure, bacterial resistance, and adverse event rates. RESULTS: Initially, 111 RGTs were identified. We excluded 81 studies due to low quality methodology. An analysis of the remaining RGTs identified therapeutic equivalence of ciprofloxacin against other antimicrobials in terms of bacterial eradication and clinical cure at the end of treatment and in subsequent stages. The percentage of bacterial resistance was similar in both groups, while the percentage of related adverse events was significantly lower in the groups treated with ciprofloxacin. CONCLUSIONS: We conclude that ciprofloxacin is a safe and effective therapeutic alternative for the treatment of acute or complicated urinary tract infections in adults.

[Efficacy of racecadotril vs. smectite, probiotics or zinc as an integral part of treatment of acute diarrhea in children under five years: A meta-analysis of multiple treatments]. / Eficacia del racecadotrilo versus smectita, probióticos o zinc como parte integral del tratamiento de la diarrea aguda en menores de cinco años: meta-análisis de tratamientos múltiples.

RATIONALE: Despite major advances in treatment, acute diarrhea continues to be a public health problem in children under five years. There is no systematic approach to treatment and most evidence is assembled comparing active treatment vs. placebo. OBJECTIVE: Systematic review of evidence on efficacy of adjuvants for treatment of acute diarrhea through a network meta-analysis. METHODS: A systematic search of multiple databases searching clinical trials related to the use of racecadotril, smectite, Lactobacillus GG, Lactobacillus reuteri, Saccharomyces boulardii and zinc as adjuvants in acute diarrhea was done. The primary endpoint was duration of diarrhea. Information is displayed through network meta-analysis.The superiority of each coadjutant was analyzed by Sucra approach. RESULTS: Network meta-analysis showed race cadotril was better when compared with placebo and other adjuvants. Sucra analysis showed racecadotril as the first option followed by smectite and Lactobacillus reuteri. INTERPRETATION: Considering a strategic decision making approach, network meta-analysis allows us to establish the therapeutic superiority of racecadotril as an adjunct for the comprehensive management of acute diarrhea in children aged less than five years.

Giardial triosephosphate isomerase as possible target of the cytotoxic effect of omeprazole in Giardia lamblia.

Giardiasis is highly prevalent in the developing world, and treatment failures with the standard drugs are common. This work deals with the proposal of omeprazole as a novel antigiardial drug, focusing on a giardial glycolytic enzyme used to follow the cytotoxic effect at the molecular level. We used recombinant technology and enzyme inactivation to demonstrate the capacity of omeprazole to inactivate giardial triosephosphate isomerase, with no adverse effects on its human counterpart. To establish the specific target in the enzyme, we used single mutants of every cysteine residue in triosephosphate isomerase. The effect on cellular triosephosphate isomerase was evaluated by following the remnant enzyme activity on trophozoites treated with omeprazole. The interaction of omeprazole with giardial proteins was analyzed by fluorescence spectroscopy. The susceptibility to omeprazole of drug-susceptible and drug-resistant strains of Giardia lamblia was evaluated to demonstrate its potential as a novel antigiardial drug. Our results demonstrate that omeprazole inhibits giardial triosephosphate isomerase in a species-specific manner through interaction with cysteine at position 222. Omeprazole enters the cytoplasmic compartment of the trophozoites and inhibits cellular triosephosphate isomerase activity in a dose-dependent manner. Such inhibition takes place concomitantly with the cytotoxic effect caused by omeprazole on trophozoites. G. lamblia triosephosphate isomerase (GlTIM) is a cytoplasmic protein which can help analyses of how omeprazole works against the proteins of this parasite and in the effort to understand its mechanism of cytotoxicity. Our results demonstrate the mechanism of giardial triosephosphate isomerase inhibition by omeprazole and show that this drug is effective in vitro against drug-resistant and drug-susceptible strains of G. lamblia.

Pulmonary tuberculous: Symptoms, diagnosis and treatment. 19-year experience in a third level pediatric hospital.

BACKGROUND: Pulmonary tuberculosis (PTB) is an infectious disease that involves the lungs and can be lethal in many cases. Tuberculosis (TB) in children represents 5 to 20% of the total TB cases. However, there are few updated information on pediatric TB, reason why the objective of the present study is to know the real situation of PTB in the population of children in terms of its diagnosis and treatment in a third level pediatric hospital. METHODS: A retrospective study based on a revision of clinical files of patients less than 18 years old diagnosed with PTB from January 1994 to January 2013 at Instituto Nacional de Pediatria, Mexico City was carried out. A probable diagnosis was based on 3 or more of the following: two or more weeks of cough, fever, tuberculin purified protein derivative (PPD) +, previous TB exposure, suggestive chest X-ray, and favorable response to treatment. Definitive diagnosis was based on positive acid-fast bacilli (AFB) or culture. RESULTS: In the 19-year period of revision, 87 children were diagnosed with PTB; 57 (65.5%) had bacteriologic confirmation with ZN staining or culture positive (in fact, 22 were ZN and culture positive), and 30 (34.5%) had a probable diagnosis; 14(16.1%) were diagnosed with concomitant disease, while 69/81 were immunized. Median evolution time was 21 days (5-150). Fever was found in 94.3%, cough in 77%, and weight loss in 55.2%. History of contact with TB was established in 41.9%. Chest X-ray showed consolidation in 48.3% and mediastinal lymph node in 47.1%. PPD was positive in 59.2%, while positive AFB was found in 51.7% cases. Culture was positive in 24/79 patients (30.4%), PCR in 20/27 (74.1%). 39 (44.8%) patients were treated with rifampin, isoniazid, and pyrazinamide while 6 (6.9%) received the former drugs plus streptomycin and 42 (48.3%) the former plus ethambutol. There were three deaths. CONCLUSIONS: PTB in pediatric population represents a diagnostic challenge for the fact that clinical manifestations are unspecific and the diagnosis is not confirmed in all cases; that is why clinical suspicion, X-ray findings and PPD are indispensable for opportune start of treatment.

Safety of a dual potential prebiotic system from Mexican agave "Metlin® and Metlos®", incorporated to an infant formula for term newborn babies: a randomized controlled trial.

RATIONALE: Infant formulae are being supplemented with probiotics, prebiotics, or symbiotic despite uncertainties regarding their efficacy. Mexican agave is an interesting source of fructans with particular features and with potential prebiotic effects. MATERIAL AND METHODS: RCT in 600 healthy term babies (20 ± 7 days), allocated to receive standard infant formula (control) or infant formula added with a dual prebiotic system "Metlin® and Metlos®", from Mexican agave. Primary outcomes include stools frequency, stools consistency, gastrointestinal intolerance (frequency of abdominal distension, flatulency, regurgitations, vomiting). Secondary outcomes include changes on weight and height along the study and frequency of dermatologic problems (eczema). RESULTS: In 66,120 days of total follow-up, there were no differences on the frequency of stools passage (Human Milk: 3.8 ± 2.4 evacuations per day; Pro + Metlin + Metlos 3.6 ± 2.0; Pro + Metlin 3.6 ± 2; only Pro 3.4 ± 2.3¸ only formula 3.4 ± 2.0; p NS). Consistency of stools was similar between human milk and prebiotics supplemented groups. Also the frequency of gastrointestinal symptoms was significantly low between these groups. CONCLUSIONS: Fructans derivate from agave and added to infant formula are safe and well tolerated by Mexican healthy term babies.